No CrossRef data available.
Article contents
Neuropsychological and sensory gating deficits related to remote alcohol abuse history in schizophrenia
Published online by Cambridge University Press: 23 January 2006
Abstract
Recent evidence suggests that changes in brain structure associated with alcohol abuse are compounded in individuals dually diagnosed with alcohol abuse and schizophrenia. To investigate the separate, and possibly interacting, effects of these diagnoses, an event-related brain potential (ERP) measure of auditory information processing (P50 sensory gating paradigm) and neuropsychological measures were administered to healthy control participants with either (1a) no history of alcohol abuse/dependence, or (1b) a remote history of alcohol abuse/dependence, and patients with schizophrenia with either (2a) no history of alcohol abuse/dependence, or (2b) a remote history of alcohol abuse/dependence. Schizophrenia was associated with impaired P50 sensory gating and poorer performance across neuropsychological scores compared to measurements in healthy control participants. Those with a positive alcohol history had impaired gating ratios in contrast to those with a negative alcohol history. There were additive effects of schizophrenia diagnosis and alcohol history for P50 sensory gating and for neuropsychological scores: attention, working memory, and behavioral inhibition. For executive attention and general memory there was an interaction, suggesting that the combination of schizophrenia and history of alcohol abuse results in greater impairment than that predicted by the presence of either diagnosis alone. (JINS, 2006, 12, 34–44.)
Keywords
Information
- Type
- Research Article
- Information
- Journal of the International Neuropsychological Society , Volume 12 , Issue 1 , January 2006 , pp. 34 - 44
- Copyright
- © 2006 The International Neuropsychological Society
INTRODUCTION
It has been estimated that as many as 9.4% of the adult population in the United States are alcohol abusers and 14.1% are alcohol dependent (Kessler et al., 1994). It is further estimated that as many as 10% of treated alcoholics have organically based mental impairment (Horvath, 1975). Even in those with no readily identifiable organicity, 50 to 85% of treated alcoholics manifest mild to moderate impairment in neuropsychological functioning (Parsons, 1986; Parsons & Nixon, 1993). Alarmingly, lifetime incidence of alcohol dependence and abuse in those with schizophrenia has been estimated to be 33.7%, a rate several times that of the general population (Regier et al., 1990). However, despite the extent of the problem, the consequences of comorbidity are little understood.
Alcohol abuse is characterized by behavioral symptoms, for example failure to fulfill role obligations at work or school, use in hazardous situations, and recurrent use despite legal problems and social problems. A diagnosis of alcohol dependence involves identifying the presence of more serious alcohol-related problems, including developing a tolerance to alcohol, the presence of withdrawal symptoms, and drinking increasingly greater amounts despite efforts to stop (American Psychiatric Association, 2004). The long-term sequelae of alcohol abuse and dependence are well documented. Neuroanatomic abnormalities secondary to chronic alcohol abuse have been noted, for example, reduced cortical (Jernigan et al., 1991; Agartz et al., 1999) and prefrontal volume (Pfefferbaum et al., 1997; Sullivan, 2003), cerebellar abnormality (Sullivan, 2003), and reduced hippocampal volume (Bergman et al., 1980; Sullivan et al., 1995; Agartz et al., 1999; Laasko et al., 2000).
More sensitive to neural abnormalities than standard clinical neuroimaging techniques, neuropsychological measures assess brain dysfunction in terms of behavioral abnormality (Lezak, 1995). Cognitive impairment in those with a history of alcoholism is well-documented (i.e., Parsons & Stevens, 1986; Parsons, 1987; Oscar-Berman & Shagrin, 1997; Moselhy et al., 2001; Brokate et al., 2003; Goldstein et al., 2004). Although considerable recovery of cognitive functioning may occur following successful abstinence (Goldman, 1995; Pfefferbaum et al., 1995), it has been estimated that mild-to-moderate neuropsychological impairment remains in 50% of abstinent alcoholics, and that there is considerable individual variability in the degree of recovery (Grant et al., 1984; Rourke & Grant, 1995; Rourke & Grant, 1999). Further, of the neuropsychological domains, general memory improves considerably in the weeks following abstinence, but impairment remains in attention and executive function, verbal ability, and information processing speed (Goldstein et al., 2004; Oscar-Berman et al., 2004; Bates et al., 2005). In a review, Pfefferbaum and colleagues (2004) remarked that studies of long-term cognitive recovery in former alcohol abusers that were presumed to be premorbidly neurologically normal have consistently shown impaired scores across measures of functions typically attributed to the frontal lobes, such as executive function, attention and working memory.
This pattern of deficits should be of particular relevance for those with schizophrenia, a disorder characterized by executive dysfunction and problem-solving deficits (Bilder et al., 1995; Neuchterlein et al., 2004), attention deficits (Heinrichs & Zakzanis, 1997; Bilder et al., 2000; Neuchterlein et al., 2004), reduced working memory capacity (Manoach, 2001), and impaired memory (Heinrichs & Zakzanis, 1997; Saykin et al., 1991). Recent comorbidity studies of alcoholism in schizophrenia have suggested an additive deleterious effect on both neuroanatomic measures and neuropsychological functioning. For example, reduced prefrontal gray matter volume was observed in patients with schizophrenia compared to control participants, and still smaller prefrontal gray matter volume was documented in patients with comorbid alcoholism and schizophrenia (Mathalon et al., 2003). Others have documented reduced pontine and thalamic volumes (Sullivan, 2003) associated with alcoholism, and have shown yet greater reductions associated with comorbidity that is not present in schizophrenia patients without comorbid alcohol abuse. In those with comorbid schizophrenia and alcoholism, additive deficits have been documented in neuropsychological domains, including executive functioning, attention, working memory, and general memory (Sullivan et al., 1997; Allen et al., 1999; Bowie et al., 2005).
A neurophysiologic measure that has been used extensively to document information processing abnormality in schizophrenia is P50 sensory gating (for a review, see Braff, 1993; Thoma et al., 2003; Hanlon et al., 2005). In a standard P50 gating protocol, the event-related brain potential (ERP) generated to each of two temporally proximate clicks is assessed at electrode Cz. A gating ratio (S2/S1) is then computed as the amplitude of the positive 50-ms component of the second click (S2) divided by the amplitude of the same component for the first click (S1). Normal control participants show a reduced P50 response following S2 compared to S1, which when expressed as a ratio typically ranges from .3 to .4. However, individuals with schizophrenia show impaired sensory gating, with ratios that are typically much higher, even approaching or exceeding 1.0. This suggests a failure to modulate the flow of incoming sensory information. Indeed, a recent study showed that impairment in neurophysiologic measures of gating is associated with increased reported experience of sensory overload in healthy control participants (Kisley et al., 2004; although negative findings in schizophrenia have been reported: see Jin et al., 1998). Although this P50 sensory gating deficit is well established in schizophrenia, the clinical correlates of the deficit have not been well documented.
The magnitude of the P50 sensory gating deficit in schizophrenia is at least equal to that of neuropsychological deficits in schizophrenia (Bramon et al., 2004) and gating may be an equally sensitive marker of alcohol abuse history (Marco et al., 2005). Further, neuroanatomic gray matter volume deficits are greatest in those with comorbid schizophrenia and alcoholism in prefrontal and superior temporal gyri (STG) regions (Mathalon et al., 2003), and it might be expected that they are reflected in measures associated with fronto-temporal function, such as P50 sensory gating (Weisser et al., 2001; Edgar et al., 2003; Grunwald et al., 2003; Huang et al., 2003; Thoma et al., 2003, 2004; Boutros et al., 2005) and neuropsychological measures of executive functioning, attention, working memory, and general memory. For the present study, it was hypothesized that participants with schizophrenia would score more poorly than control participants across measures of cognitive functioning and have poorer P50 gating. Further, it was hypothesized that participants with an alcohol abuse history would have poorer gating and neuropsychological function than those without such a history. Based on evidence that dual diagnosis may result in greater impairment than that associated with either diagnosis alone, it was further hypothesized that there would be an interaction of alcohol abuse history and schizophrenia diagnoses such that those with schizophrenia who abuse alcohol would have the most profound deficits, with the interaction of diagnoses resulting in deficits greater than either schizophrenia or alcohol abuse diagnoses alone.
METHODS
Research Participants
Of 18 patients with schizophrenia, 9 had an alcohol abuse history. Of 17 control participants, 8 had an alcohol abuse history. Group membership was determined with the Structured Clinical Interview for DSM-IV, Clinician Version (SCID-CV, First et al., 1996). Groups were matched for age, education, and sex. No participant had a history of head injury, neurological disorder, or severe medical illness. Demographic characteristics of the groups are listed in Table 1.
Group demographics
The schizophrenia group consisted of volunteers and referrals who were relatively stable patients, well known to their providers. They met predetermined criteria for clinical stability, as they had been treated with the same antipsychotic medications for at least three months and had no inpatient stays during the last year. Absence of other current psychiatric disorders was determined using the SCID-CV. Patients with schizophrenia were all taking antipsychotic medications, either haloperidol, prolixin, olanzapine, risperidone, clozapine, aripiprazole, or quetiapine. Antipsychotic medications, categorized in terms of either novel or conventional antipsychotics, are listed in Table 2 for both the schizophrenia/ETOH positive and the schizophrenia/ETOH negative groups.
Antipsychotic medications by category
The control group consisted of healthy volunteers recruited via advertisements in local newspapers. Control participants were screened for the presence of Axis-I and Axis-II psychopathology via (1) a comprehensive structured clinical interview with a licensed clinical psychologist (Dr. Thoma) or with a psychology graduate student under his direct supervision, (2) SCID-CV, and if there was a question of the presence of schizotypal or schizoid symptoms following these procedures, (3) their scores on the Social Anhedonia Scale (Chapman et al., 1994) and the Magical Ideation Scale (Eckblad & Chapman, 1983) were reviewed. During the clinical interview, potential control participants were asked if they had a first-degree relative with schizophrenia or other psychotic disorder, and if so, were not included in the study.
Participants in the ETOH positive groups met DSM-IV criteria for alcohol abuse or dependence for a significant period (>18 months) at some time in the past. Most participants met the more stringent criteria for alcohol dependence, but this distinction was not used in the present analyses. For most participants, abuse history refers to very remote history (>5 years ago). Although some participants met criteria more recently, none did more recently that 1 year prior to this study. Potential participants who met criteria for alcohol abuse or dependence more recently than 1 year prior were screened from the study. If acute substance use was evident at the time of data collection, a urine sample was obtained prior to data collection and participants were not included in the study if a positive result was found. However, these procedures were not necessary during the current data collection and no participants were screened from the study. Data were also gathered regarding use of other substances of abuse; listed in Table 3 are the numbers of participants reporting past use. A minority of the present sample overlapped with that of Thoma et al. (2003), 5 patients and 8 controls.
Drugs of abuse
Institutional Review Board approval was obtained prior to running participants, and participants were informed that they could leave the study at any time. Appropriate informed consent was obtained from participants and/or patients' guardians when pertinent.
Auditory Paired-Click Design
The auditory paired-click design consists of pairs of clicks separated by a 500-ms interstimulus interval (ISI). This ISI has been shown to provide maximum differentiation between the gating capacities of normal and schizophrenia patients (Nagamoto et al., 1989). The pairs were repeated using an intertrial interval (ITI) that varied randomly from 7 to 10 seconds in 1-sec increments. Stimuli were binaural 3-ms clicks, created and delivered using NeuroStim software through Etymotic earphones placed bilaterally in the participant's ear canal. Prior to data collection, each participant's hearing threshold was determined and peak click intensity was set 30 dB above threshold. To minimize motion-related noise artifacts produced by the plastic tubes connected to the earphones, the plastic tubes were taped to the participant's face and tape was placed over the ear. One hundred and fifty paired-click uncontaminated epochs were collected, with each session lasting approximately 30 minutes.
EEG Data Collection
EEG data were collected at the Albuquerque VA Center for Functional Brain Imaging, using a 24-channel electrode cap with silver/silver-chloride electrode placements that included the 19 standard sites in a cap that approximated the international 10-20 system (Jasper, 1958). Each scalp electrode was referenced to the right ear lobe during recording and rereferenced off-line to bilateral ear lobes. One channel of vertical and one channel of horizontal electo-occulograph (EOG) data were recorded, and trials were rejected in which EOG and EEG peak-to-peak signal strength exceeded 150 μV in any channel. Electrode impedances were kept below 10 kOhms. Data were collected by using Syn-Amps controlled through the SCAN software package (Neuroscan, El Paso, TX). Data were filtered on-line using an analog bandpass filter of 0.03–150 Hz and digitized at 500 Hz per channel for 800 ms beginning 300 ms prior to S1 and ending 500 ms after S2. One hundred and fifty uncontaminated click-pair epochs were collected, with the overall session lasting approximately 30 minutes. Participants were instructed to stay still during the recording procedure and to blink in between pairs of clicks as a means to reduce ocular or muscular artifact. Prior to averaging, epochs were rejected during off-line visual inspection if eye-blink artifact, excessive alpha-band, or delta-band activity were detected.
P50 Sensory Gating Measurement
Stimuli were pairs of binaural 3-ms clicks created and delivered using NeuroStim software. For P50 peak scoring, cross-trial average ERPs were digitally filtered using Chebyshev Type 2 IIR filters with a 4-point moving-average and a recursive high-pass filter (A = 0.85). Filter parameters were: Fstop = 1 Hz, Fpass = 4 Hz for the high-pass and Fstop = 60 Hz, Fpass = 55 Hz for the low-pass. The ripple for the pass band (4–55 Hz) was less than 1 dB, and signal loss for the stop bands (<1 and >60 Hz) was more than 60 dB. Each filter was applied twice, in the forward and reverse direction, to increase roll-off and to preserve waveform latency by avoiding the introduction of a phase shift, for example. The prestimulus baseline (−100 to −10 ms) was removed. P50 was defined as the most positive peak at Cz between 40 and 80 ms after S1 onset. If two equal-amplitude peaks were present, the later peak was scored. S1 amplitude was calculated as the difference between the positive peak and immediately preceding negative trough. This trough did not have a latency of less than 30 ms following S1 onset (i.e., the trough search was stopped if a horizontal tangent line was not encountered by 30 ms poststimulus, and the 30-ms point was then used as the start of the P50 component). For the S2 score, the most positive point at Cz following S2 onset within +/− 10 ms of the latency of the S1 P50 peak was selected. This range ensured that the same response was measured for S1 and S2. As with S1, the S2 score was calculated relative to the immediately preceding negative trough. P50 gating ratio was calculated as S2 amplitude divided by S1 amplitude. Figure 1 shows examples of P50 responses to S1 and S2 in a control participant and in a patient with schizophrenia.
Panel 1a: An ERP waveform depicting normal P50 sensory gating in a selected control participant. For this participant, the peak of the P50 response to the first stimulus (S1) occurs at 62.3 ms and is 2.20 μV in amplitude. The peak of the P50 response to the second stimulus (S2) occurs at 62.3 ms and is 0.80 μV in amplitude. Thus, the P50 sensory gating ratio (S2/S1) would be .36, reflecting normal gating. Panel 1b: An ERP waveform depicting abnormal sensory gating in a patient with schizophrenia. The peak of the P50 response to the first stimulus (S1) occurs at 59.8 ms and is 2.70 μV in amplitude. The peak of the P50 response to the second stimulus (S2) occurs at 59.8 ms and is 2.07 μV in amplitude. Thus, the sensory gating ratio (S2/S1) would be .77, indicating impaired gating.
Neuropsychological Test Battery
A brief neuropsychological battery was devised to assess a range of neuropsychological domains, and to test those domains expected to be impaired in those with schizophrenia and with ETOH histories, such as attention, working memory, general memory, and executive functioning. The battery was also designed to fit time constraints imposed by a relatively rigorous neuroimaging session. Included in this battery were the Shipley Institute for Living Scale (Zachary, 1967), the Connors' Continuous Performance Test (CPT; Connors, 1994), the Digit Span, Logical Memory, and Visual Reproduction subtests from the Wechsler Memory Scale–Revised (WMS–R; Wechsler, 1987), the Auditory Consonant Trigrams Test (ACT; Spreen & Strauss, 1988), and the Trail Making Test, Parts A and B (Reitan & Wolfson, 1971). Neuropsychological Domain scores were created by standardizing (z scoring) test scores across groups (except Shipley, see later) and then summing them for each participant as follows: (1) Attention (CPT d′ + Digit Span Forward); (2) Working Memory (ACT + Digit Span Backward); (3) Executive Attention (Trail Making Test, Part A + Trail Making Test, Part B); (4) Behavioral Inhibition (CPT, False Alarm Rate); and (5) General Memory (Wechsler Memory Scale LM I + LM II + VR I + VR II).
Neither the Shipley estimated WAIS-R IQ score, nor the raw Shipley subtest scores were included in the neuropsychological domain scores because there is evidence that measures of intellectual functioning, particularly of crystallized intelligence as measured on tests of vocabulary, may not be sensitive to neuropsychological deficits. As such, it is often used as a test of premorbid functioning, and thus was considered separately.
Schizophrenia Symptom Assessment
The Positive and Negative Syndrome Scale (PANSS; Kay et al., 1987) and the Schedule for the Assessment of Negative Symptoms (SANS; Andreasen, 1982), administered by trained and reliable raters, were used to assess positive and negative symptoms. Depression was assessed with the Calgary Depression Scale for Schizophrenia (Calgary; Addington et al., 1990). Movement/motor symptoms were assessed with the Abnormal Involuntary Movement Scale (AIMS; Guy, 1976) and the Simpson-Angus Scale (SAS; Simpson & Angus, 1970).
RESULTS
Due to signal-to-noise issues (e.g., would dental work and excessive movement hurt EEG, or is this from MEG?) EEG data were not usable from 6 participants whose data were included in the neuropsychological testing results. Two of those were from the Control/Positive ETOH group (resulting in an N of 6), two were from the Schizophrenia/Negative ETOH group (resulting in an N of 7), and two were from the Schizophrenia/Positive ETOH group (resulting in an N of 7). Thus, the analysis of EEG data was on a smaller sample than that for the neuropsychological study.
To investigate the effect of both schizophrenia diagnosis and history of alcohol abuse, analyses of variance (ANOVAs) were conducted with Schizophrenia/Control Group and Positive ETOH/Negative ETOH Abuse History Group as independent variables. The dependent variables fell into three categories: P50 Gating Ratio, Neuropsychological Domain Scores, and Shipley Vocabulary Score. Although there were no hypotheses specifically regarding P50 latency and amplitude measures, these variables were also investigated, in separate ANOVAs, as possible contributors to the gating effect.
In the P50 Gating Ratio ANOVA, there was a main effect for Schizophrenia/Control Group (F(1,25) = 10.69, p = .004), showing patients with schizophrenia as having poorer gating than normal controls. There was also a main effect for ETOH Abuse History (F(1,25) = 7.92, p = .01), those with a Positive ETOH history having poorer gating than those with a Negative ETOH history. The interaction was nonsignificant (see Figure 2). The observed power for Schizophrenia diagnosis indicated a large effect size (γ = .88), as did that for ETOH Abuse History (γ = .77), however, the effect size for their interaction was very small (γ = .09). Groups were equivalent on measures of P50 amplitude and latency, with one exception, patients with schizophrenia had larger S2 amplitudes (F(1,25) = 2.13, p = .04).
Bars represent group mean P50 Auditory Sensory Gating Ratios (S2/S1), error bars represent standard deviation. Abbreviations: Con/Neg ETOH = Control/Negative ETOH; Con/Pos ETOH = Control/Positive ETOH; Schiz/Neg ETOH = Schizophrenia/Negative ETOH; Schiz/Pos ETOH = Schizophrenia/Positive ETOH.
Separate ANOVAs were conducted for each of the Neuropsychological Domain Scores: (1) For the Attention Score, patients with schizophrenia scored more poorly than normal controls (F(1,34) = 4.94, p = .03), but there was no effect for ETOH history, nor was there a significant interaction. (2) There was a cumulative effect for Schizophrenia diagnosis and positive ETOH history on the Working Memory Score; patients with schizophrenia scored more poorly than controls (F(1,34) = 15.42, p < .001), and participants with a positive ETOH history scored more poorly than those with a negative ETOH history (F(1,34) = 4.20, p = .05), but the interaction was nonsignificant. (3) For the Executive Attention Score, patients with schizophrenia scored more poorly than control participants (F(1,34) = 22.22, p < .001), and those with a positive ETOH history scored more poorly than those with a negative ETOH history (F(1,34) = 8.67, p = .006). There was also a trend toward a significant interaction (F(1,34) = 3.78, p = .06), suggesting greater impairment for those with dual diagnoses than for those with either Schizophrenia or ETOH positive diagnosis alone (see Figure 3). (4) For the Behavioral Inhibition Score, patients with schizophrenia scored more poorly than control participants (F(1,34) = 5.20, p = .03), but there was no effect for ETOH history, nor was the interaction significant. (5) For the General Memory Score, patients with schizophrenia scored more poorly than control participants (F(1,34) = 32.68, p < .001). While there was no main effect for ETOH history, there was a significant interaction F(1,34) = 5.59, p = .03), indicating that there was no effect for ETOH history for the control participants, but there was a significant effect for patients with schizophrenia (see Figure 4).
Bars represent group mean Executive Attention Domain Scores (summed z scores), error bars represent standard deviation.
Bars represent group mean General Memory Domain Scores, error bars represent standard deviation.
Impairment was also evident in individual neuropsychological test scores. Raw scores on neuropsychological measures and the extent of impairment with respect to the Control/Negative ETOH Group is presented in Table 4.
Neuropsychological test group means and significance from control/negative ETOH
In the Shipley Vocabulary Score ANOVA, patients with schizophrenia had lower scores than control participants (F(1,34) = 7.98, p = .008). There was no effect for ETOH History and no interaction. Subgroup comparisons revealed no difference between the Control/Positive ETOH Group and the Control/Negative ETOH Group. The Control/Positive ETOH Group scored higher than the Schizophrenia/Negative ETOH Group (t = 2.12, p = .04). There was no difference between the Schizophrenia/Negative ETOH and Schizophrenia/Positive ETOH Groups.
There were no ETOH Positive/ETOH Negative Group differences found for any schizophrenia symptom measure, including positive symptoms, negative symptoms, and depression (PANSS, SANS, Calgary), nor for the movement scale scores (AIMS, SAS).
No bivariate correlations between P50 Sensory Gating Ratio and any neuropsychological summary scores approached significance for any group.
DISCUSSION
Auditory sensory gating is impaired in schizophrenia and has been shown to be related to neuropsychological measures of attention and working memory (Yee & White, 2001; Thoma et al., 2003). Present analyses are consistent with the finding of impaired gating in patients with schizophrenia overall, with patients demonstrating higher gating ratios compared to an age- and education-matched control group. Participants with a history of alcohol abuse and dependence, regardless of Schizophrenia/Control Group membership, also exhibited a higher (more impaired) gating ratio. Thus, the effect of dual diagnosis on P50 sensory gating was additive, leaving those with a history of dual diagnosis most severely affected. Interestingly, there was a similar degree of gating impairment associated with each diagnostic classification.
Alcohol abuse history has not been consistently related to P50 sensory gating. For example, Boutros and colleagues (2000) showed moderately (but not statistically significant) impaired P50 sensory gating in participants with current diagnoses of alcohol dependence in a study with roughly the same group size (10 participants per group). However, the alcohol-dependent participants met DSM-IV criteria for alcohol dependence at the time of the study, whereas the present study used participants who met criteria for a period in the remote past (but did not currently meet criteria). Fein et al. (1996) found no statistically significant effect for alcohol abuse history on P50 gating, but mean gating ratios were higher in the alcohol group, suggesting that this study did not have the statistical power to show the effect. The present study, which matched for age and education, may have better controlled potentially confounding variables. More recently, Marco et al. (2005) demonstrated impaired gating ratios in an alcoholism group with a history notable for duration of alcohol dependence for more than 4 years.
Acute administration of alcohol causes a decrease in P50 amplitude, suggesting an acute effect on the neural system associated with early auditory information processing, and an increase in P50 gating ratio (Freedman et al., 1987). Chronic exposure to alcohol may have more lasting effects on that system. Chronic alcohol use is related to reduced size of brain regions such as hippocampus (Laasko et al., 2000; Sullivan et al., 1995), prefrontal cortex (Pfefferbaum et al., 1997), and superior temporal gyrus (STG) (Mathalon et al., 2003), and a deficit in those regions is known to affect neuropsychological functioning and sensory modulation (Knight et al., 1999; Thoma et al., 2004). The finding of increasingly impaired attention, working memory, and executive functioning across the current experimental groups is consistent with studies showing cumulative deficits in cortical structure and function in regions supporting successful gating of auditory stimuli (e.g., Mathalon et al., 2003).
Those with a schizophrenia diagnosis were impaired compared to control participants across all neuropsychological domains. Those with a history of alcohol abuse/dependence were impaired specifically in working memory and executive attention. However, those with comorbid schizophrenia and alcohol abuse/dependence histories had greater impairment in executive attention than that predicted by a simple additive effect, consistent with our hypothesis of increased susceptibility to alcohol-related cognitive impairment in those with schizophrenia. General memory was unaffected by ETOH positive diagnosis across the control groups, but for patients with schizophrenia, memory was worse for those with an ETOH positive history than for those without, again consistent with a particular susceptibility in schizophrenia.
Because the Vocabulary Subtest raw score derived from the Shipley Institute for Living Scale is generally considered to be a reliable estimate of premorbid cognitive function (Lezak, 1995), group comparisons on that measure were done to address the question of possible causal precedence between alcohol abuse and information processing deficits. The Positive and Negative ETOH Groups, equivalent on education and age, were also equivalent on this presumed measure of premorbid functioning, suggestive of higher premorbid ability in the Positive ETOH group. This is consistent with the notion that the neuropsychological deficit associated with ETOH positive group membership was secondary to alcohol abuse rather than the reverse.
Small group size and retrospective data limit the conclusions drawn from the present results. However, these analyses support the hypotheses that patients with schizophrenia have impaired gating in general and that they are particularly susceptible to the deleterious effect of alcohol on the central nervous system. Further, in both controls and schizophrenia patients, P50 sensory gating appears to be a sensitive indicator of information-processing abnormality associated with alcohol abuse.
ACKNOWLEDGMENTS
The authors wish to thank Jeanne Schneider for administrative support and Dr. Fernando Torres for assistance with diagnostic evaluation of participants. This research was supported by a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award to Dr. Thoma and NIMH R01-65304 and Mental Illness and Neuroscience Discovery (MIND) Institute Grant # 2204 to Dr. Cañive.
References
REFERENCES
Addington, D.,
Addington, J., &
Schissel, B.
(1990).
A depression rating scale for schizophrenics.
Schizophrenia Research,
3,
247–251.Google Scholar
Agartz, I.,
Momenan, R.,
Rawlings, R.R.,
Kerich, M.J., &
Hommer, D.W.
(1999).
Hippocampal volume in patients with alcohol dependence.
Archives of General Psychiatry,
56,
356–363.CrossRefGoogle Scholar
Allen, D.N.,
Goldstein, G., &
Aldarondo, F.
(1999).
Neurocognitive dysfunction in patients diagnosed with schizophrenia
and alcoholism.
Neuropsychology,
13,
62–68.Google Scholar
American Psychiatric Association.
(2004).
Diagnostic and Statistical Manual of Mental Disorders
(4th ed., text revision: DSM-IV-TR).
Washington, DC:
American Psychiatric Association.
Andreasen, N.C.
(1982).
Negative symptoms in schizophrenia: Definition and
reliability.
Archives of General Psychiatry,
39,
784–788.CrossRefGoogle Scholar
Bates, M.E.,
Voelbel, G.T.,
Buckman, J.F.,
Labouvie, E.W., &
Barry, D.
(2005).
Short-term neuropsychological recovery in clients with substance use
disorders.
Alcoholism: Clinical and Experimental Research,
29,
367–377.CrossRefGoogle Scholar
Bergman, H.,
Borg, S.,
Hindermarsh, T.,
Idestrom, O.M., &
Mutzell, S.
(1980).
Computed tomography of the brain and neuropsychological assessment
of male alcoholic patients and a random sample form the general male
population.
Acta Psychiatra Scandinavica,
62 (Suppl. 286),
47–56.Google Scholar
Bilder, R.M.,
Bogerts, B.,
Ashtari, M.,
Wu, H.W.,
Alvir, J.M.,
Jody, D.,
Reiter, G.,
Bell, L., &
Lieberman, J.A.
(1995).
Anterior hippocampal volume reductions predict frontal lobe
dysfunction in first-episode schizophrenia.
Schizophrenia Research,
17,
47–58.CrossRefGoogle Scholar
Bilder, R.M.,
Goldman, R.S.,
Robinson, D.,
Reiter, G.,
Bell, L.,
Bates, J.A.,
Pappadopulos, E.,
Wilson, D.,
Alvir, J.,
Woerner, M.,
Geisler, S.,
Kane, J., &
Lieberman, J.A.
(2000).
Neuropsychology of first episode schizophrenia: Initial
characterization and clinical outcome.
American Journal of Psychology,
157,
549–559.CrossRefGoogle Scholar
Bowie, C.R.,
Serper, M.R.,
Riggio, S., &
Harvey, P.D.
(2005).
Neurocognition, symptomatology, and functional skills in older
alcohol-abusing schizophrenia patients.
Schizophrenia Bulletin,
31,
175–182.Google Scholar
Boutros, N.N.,
Reid, C.M.,
Petrakis, I.,
Campbell, D.,
Torello, M., &
Krystal, J.
(2000).
Similarities in the disturbances in cortical information processing
in alcoholism and aging: A pilot evoked potential study.
International Psychogeriatrics,
12,
513–525.CrossRefGoogle Scholar
Boutros, N.N.,
Trautner, P.,
Rosburg, T.,
Korzyukov, O.,
Grunwald, T.,
Schaller, C.,
Elger, C.E., &
Kurthen, M..
(2005).
Sensory Gating in the Human Hippocampal and Rhinal Regions.
Clinical Neurophysiology,
116,
1967–1974.Google Scholar
Braff, D.L.
(1993).
Information processing and attention dysfunctions in
schizophrenia.
Schizophrenia Bulletin,
19,
233–259.CrossRefGoogle Scholar
Bramon, E.,
Rabe-Hesketh, S.,
Sham, P.,
Murray, R.M., &
Frangou, S.
(2004).
Meta-analysis of the P300 and P50 waveforms in schizophrenia.
Schizophrenia Research,
70,
315–329.CrossRefGoogle Scholar
Brokate, B.,
Hildebrandt, H.,
Eling, P.,
Fichtner, H.,
Runge, K., &
Timm, C.
(2003).
Frontal lobe dysfunctions in Korsakoff's syndrome and chronic
alcoholism: Continuity or discontinuity?
Neuropsychology,
17,
420–428.Google Scholar
Chapman, L.J.,
Chapman, J.P.,
Kwapil, T.R., &
Eckblad, M.
(1994).
Putatively psychosis-prone subjects 10 years later.
Journal of Abnormal Psychology,
103,
171–183.Google Scholar
Connors, C.K.
(1994).
The Connors' Continuous Performance Test Computer Program 3.0
user manual.
Toronto:
Toronto Multi-health systems.
Eckblad, M.L. &
Chapman, L.J.
(1983).
Magical ideation as an indicator of schizotypy.
Journal of Consulting and Clinical Psychology,
51,
215–225.CrossRefGoogle Scholar
Edgar, J.C.,
Huang, M.X.,
Weisend, M.P.,
Sherwood, A.,
Miller, G.A.,
Adler, L.E., &
Cañive, J.M.
(2003).
Interpreting abnormality: An EEG and MEG study of P50 and the
auditory paired-stimulus paradigm.
Biological Psychology,
65,
1–20.Google Scholar
Fein, G.,
Biggins, C., &
MacKay, S.
(1996).
Cocaine abusers have reduced auditory P50 amplitude and suppression
compared to both normal controls and alcoholics.
Biological Psychiatry,
39,
955–965.CrossRefGoogle Scholar
First, M.B.,
Spitzer, R.L.,
Gibbon, M., &
Williams, J.B.W.
(1996).
Structured Clinical Interview for DSM-IV Axis I Disorders (SCID),
Clinician Version.
Washington, DC:
American Psychiatric Press.
Freedman, R.,
Waldo, M.,
Waldo, C.I., &
Wilson, J.R.
(1987).
Genetic influences on auditory evoked potentials.
Alcohol,
4,
249–253.Google Scholar
Goldman, M.S.
(1995).
Recovery of cognition functioning in alcoholics: The relationship to
treatment.
Alcohol Health and Research World,
19,
148–154.Google Scholar
Goldstein, R.Z.,
Leskovjan, A.C.,
Hoff, A.L.,
Hitzemann, R.,
Bashan, F.,
Khalsa, S.S.,
Wang, G.,
Fowler, J.S., &
Volkow, N.D.
(2004).
Severity of neuropsychological impairment in cocaine and alcohol
addiction: Association with metabolism in the prefrontal cortex.
Neuropsychologia,
42,
1447–1458.Google Scholar
Grant, I.,
Adams, K., &
Reed, R.
(1984).
Aging, abstinence and medical risk factors in the prediction of
neuropsychological deficit among long-term alcoholics.
Archives of General Psychiatry,
41,
710–718.CrossRefGoogle Scholar
Grunwald, T.,
Boutros, N.N.,
Pezer, N.,
von Oertzen, J.,
Fernandez, G.,
Schaller, C., &
Elger, C.E.
(2003).
Neuronal substrates of sensory gating within the human brain.
Biological Psychiatry,
53,
511–519.CrossRefGoogle Scholar
Guy, W.
(1976).
Abnormal Involuntary Movement Scale (AIMS). ECDEU assessment manual
for psychopharmacology
(revised ed.).
Washington, DC:
U.S. Department of Health, Education and Welfare.
Hanlon, F.M.,
Miller, G.A.,
Thoma, R.J.,
Irwin, J.,
Jones, A.,
Moses, S.N.,
Huang, M.,
Weisend, M.P.,
Paulson, K.M.,
Edgar, C.,
Adler, L.E., &
Cañive, J.M.
(2005).
Distinct M50 and M100 auditory gating deficits in
schizophrenia.
Psychophysiology,
42,
417–427.CrossRefGoogle Scholar
Heinrichs, R.W. &
Zakzanis, K.K.
(1997).
Neurocognitive deficits in schizophrenia: A quantitative review of
the evidence.
Neuropsychology,
12,
426–445.Google Scholar
Horvath, T.B.
(1975).
Clinical spectrum and epidemiological features of alcoholic
dementia. In
G. Rankin (Ed.),
Alcohol, Drugs and Brain Damage.
Toronto:
Addiction Research Foundation.
Huang, M.X.,
Edgar, J.C.,
Thoma, R.J.,
Hanlon, F.M.,
Moses, S.N.,
Lee, R.R.,
Paulson, K.M.,
Weisend, M.P.,
Irwin, J.G.,
Bustillo, J.R.,
Adler, L.E.,
Miller, G.A., &
Cañive, J.M.
(2003).
Predicting EEG responses using MEG sources in superior temporal
gyrus reveals source asynchrony in patients with schizophrenia.
Clinical Neurophysiology,
114,
835–850.Google Scholar
Jasper, H.H.
(1958).
The ten-twenty electrode system of the International
Federation.
Electroencephalgraphy and Clinical Neurophysiology,
10,
371–375.Google Scholar
Jernigan, T.L.,
Butter, N.,
DiTraglia, G.,
Schafer, K.,
Smith, T.,
Irwin, M.,
Grant, I.,
Schukit, M., &
Cermak, L.S.
(1991).
Reduced cerebral gray matter observed in alcoholics using magnetic
resonance imaging.
Alcoholism: Clinical and Experimental Research,
15,
418–427.Google Scholar
Jin, Y.,
Bunney, W.E.Jr.,
Sandman, C.A.,
Patterson, J.V.,
Fleming, K.,
Moenter, J.R.,
Kalali, A.H.,
Hetrick, W.P., &
Potkin, S.G.
(1998).
Is P50 suppression a measure of sensory gating in
schizophrenia?
Biological Psychiatry,
43,
873–878.Google Scholar
Kay, S.R.,
Fiszbein, A., &
Opler, L.A.
(1987).
The Positive and Negative Syndrome Scale (PANSS) for
schizophrenia.
Schizophrenia Bulletin,
13,
261–276.Google Scholar
Kessler, R.C.,
McGonagle, K.A.,
Zhao, S.,
Nelson, C.,
Hughes, M.,
Eshleman, S.,
Wittchen, H., &
Kendler, K.S.
(1994).
Lifetime and 12-month prevalence of DSM-III-R Psychiatric Disorders
in the United States: Results from the National Comorbidity Study.
Archives of General Psychiatry,
51,
8–19.Google Scholar
Kisley, M.A.,
Noecker, T.L., &
Guinther, P.M.
(2004).
Comparison of sensory gating to mismatch negativity and
self-reported perceptual phenomena in healthy adults.
Psychophysiology,
41,
604–612.CrossRefGoogle Scholar
Knight, R.T.,
Staines, W.R.,
Swick, D., &
Chao, L.L.
(1999).
Prefrontal cortex regulates inhibition and excitation in distributed
neural networks.
Acta Psychological,
101,
159–178.CrossRefGoogle Scholar
Laasko, M.P.,
Vaurio, O.,
Savolainen, L.,
Repo, E.,
Soininen, H.,
Aronen, H.J., &
Tiihonen, J.
(2000).
A volumetric MRI study of the hippocampus in type 1 and 2
alcoholism.
Behavioural Brain Research,
109,
177–186.Google Scholar
Lezak, M.D.
(1995).
Neuropsychological assessment
(3rd ed.).
New York:
Oxford University Press.
Manoach, D.S.
(2001).
Prefrontal cortex dysfunction during working memory performance in
schizophrenia: Reconciling discrepant findings.
Schizophrenia Research,
60,
285–298.Google Scholar
Marco, J.,
Luentemilla, L., &
Grau, C.
(2005).
Auditory sensory gating deficit in abstinent chronic
alcoholics.
Neuroscience Letters,
375,
174–177.Google Scholar
Mathalon, D.H.,
Pfefferbaum, A.,
Lim, K.O.,
Rosenbloom, M.J., &
Sulluvan, E.V.
(2003).
Compounded brain volume deficits in schizophrenia-alcohol
comobidity.
Archives of General Psychiatry,
60,
245–252.CrossRefGoogle Scholar
Moselhy, H.F.,
Georgiou, G., &
Kahn, A.
(2001).
Frontal lobe changes in alcoholism: A review of the
literature.
Alcohol,
36(5),
357–368.CrossRefGoogle Scholar
Nagamoto, H.T.,
Adler, L.E.,
Waldo, M.C., &
Freedman, R.
(1989).
Sensory gating in schizophrenics and normal controls: Effects of
changing stimulation interval.
Biological Psychiatry,
25,
549–561.Google Scholar
Neuchterlein, K.H.,
Barch, D.M.,
Gold, J.M.,
Goldberg, T.E.,
Green, M.F., &
Heaton, R.K.
(2004).
Identification of separable cognitive factors in
schizophrenia.
Schizophrenia Research,
72,
29–39.CrossRefGoogle Scholar
Oscar-Berman, M.,
Kirkley, S.M.,
Gansler, D.A., &
Couture, A.
(2004).
Comparisons of Korsakoff and non-Korsakoff alcoholics on
neuropsychological tests of prefrontal brain functioning.
Alcoholism: Clinical and Experimental Research,
28,
667–675.Google Scholar
Oscar-Berman, M. &
Shagrin, B.
(1997).
Impairments of brain and behavior.
Alcohol Health & Research World,
21,
65–76.Google Scholar
Parsons, O.A.
(1986).
Cognitive functioning in sober social drinkers: A review and
critique.
Journal of Studies on Alcohol,
47,
101–114.Google Scholar
Parsons, O.A.
(1987).
Alcoholic's neuropsychological impairment.
Annals of Behavioral Medicine: A Publication of the Society of
Behavioral Medicine,
8,
13–19.Google Scholar
Parsons, O.A. &
Stevens, L.
(1986).
Previous alcohol intake and residual cognitive deficits in
detoxified alcoholics and animals.
Alcohol,
21,
137–157.Google Scholar
Parsons, O.A. &
Nixon, S.J.
(1993).
Neurobehavioral sequalae of alcoholism.
Neurologic Clinics,
11,
205–218.Google Scholar
Pfefferbaum, A.,
Sullivan, E.V.,
Mathalon, D.H.,
Shear, P.K.,
Rosenbloom, M.J., &
Lim, K.O.
(1995).
Longitudinal changes in magnetic resonance imaging brain volumes in
abstinent and relapsed alcoholics.
Alcoholism, Clinical and Experimental Research,
19,
1177–1191.CrossRefGoogle Scholar
Pfefferbaum, A.,
Sullivan, E.V.,
Mathalon, D.H., &
Lim, K.O.
(1997).
Frontal lobe volume loss observed with magnetic resonance imaging in
older chronic alcoholics.
Alcoholism: Clinical and Experimental Research,
21,
521–528.CrossRefGoogle Scholar
Pfefferbaum, A.,
Rosenbloom, M.J.,
Serventi, K.L., &
Sullivan, E.V.
(2004).
Brain volumes, RBC status, and hepatic function in alcoholics after
1 and 4 weeks of sobriety: Predictors of outcome.
American Journal of Psychiatry,
161,
1190–1196.Google Scholar
Regier, D.A.,
Farmer, M.E.,
Rae, D.S.,
Locke, B.Z.,
Keith, S.J.,
Judd, L.L., &
Goodwin, F.K.
(1990).
Comorbidity of mental disorders with alcohol and other drug abuse:
Results from the epidemiologic catchment area (ECA) study.
Journal of the American Medical Association,
264,
2511–2518.Google Scholar
Reitan, R.M. &
Wolfson, D.
(1971).
The Halstead-Reitan Neuropsychological Test Battery.
Tucson, AZ:
Neuropsychology Press.
Rourke, S.B. &
Grant, I.
(1995).
Neuropsychological deficits in male alcoholics: Part II. Using
clinical ratings to delineate the effects of interim drinking and length
of abstinence on the prevalence of deficits.
Journal of the International Neuropsychological Society,
1,
327.Google Scholar
Rourke, S.B. &
Grant, I.
(1999).
The interactive effects of age and length of abstinence on the
recovery of neuropsychological functioning in chronic male alcoholics: A
2-year follow-up study.
Journal of the International Neuropsychological Society,
5,
234–246.Google Scholar
Saykin, A.J.,
Gur, R.C.,
Gur, R.E.,
Mozley, P.D.,
Mozley, L.H.,
Resnick, S.M.,
Kester, D.B., &
Stafiniak, P.
(1991).
Neuropsychological function in schizophrenia: Selective impairment
in memory and learning.
Archives of General Psychiatry,
48,
618–624.Google Scholar
Simpson, G.M. &
Angus, J.W.S.
(1970).
A rating scale for extrapyramidal side effects.
Acta Psychiatra Scandanavica,
Supplementum
212,
11–19.CrossRefGoogle Scholar
Spreen, O. &
Strauss, E.
(1988).
A compendium of neuropsychological tests
(2nd ed.).
New York:
Oxford University Press.
Sullivan, E.V.
(2003).
Compromised pontocerebellar and cerebellothalamocortical systems:
Speculations on their contributions to cognitive and motor impairments in
nonamnesiac alcoholism.
Alcoholism: Clinical and Experimental Research,
27,
1409–1419.Google Scholar
Sullivan, E.V.,
Marsh, L.,
Mathalon, D.H.,
Lim, K.O., &
Pfefferbaum, A.
(1995).
Anterior hippocampal volume deficits in nonamnestic, aging chronic
alcoholics.
Alcoholism: Clinical and Experimental Research,
19,
110–122.CrossRefGoogle Scholar
Sullivan, E.V.,
Shear, P.K.,
Zipursky, R.B.,
Sagar, H.J., &
Pfefferbaum, A.
(1997).
Patterns of content, contextual, and working memory impairments in
schizophrenia and nonamnesic alcoholism.
Neuropsychology,
11,
195–206.CrossRefGoogle Scholar
Thoma, R.J.,
Hanlon, F.M.,
Moses, S.N.,
Edgar, J.C.,
Huang, M.,
Weisend, M.P.,
Irwin, J.,
Sherwood, A.,
Paulson, K.,
Bustillo, J.,
Adler, L.E.,
Miller, G.A., &
Cañive, J.M.
(2003).
Lateralization of auditory sensory gating and neuropsychological
dysfunction in schizophrenia.
American Journal of Psychiatry,
160,
1595–1605.CrossRefGoogle Scholar
Thoma, R.J.,
Hanlon, F.M.,
Sanchez, N.,
Weisend, M.P.,
Huang, M.,
Jones, A.,
Miller, G.A., &
Cañive, J.M.
(2004).
Auditory sensory gating deficit and cortical thickness in
schizophrenia.
Neurology and Clinical Neurophysiology,
62,
1–7.Google Scholar
Wechsler, D.
(1987).
Manual for the Wechsler Memory Scale–Revised.
San Antonio, TX:
Psychological Corporation.
Weisser, R.,
Weisbrod, M.,
Roehrig, M.,
Rupp, A.,
Schroeder, J., &
Scherg, M.
(2001).
Is frontal lobe involved in the generation of auditory evoked
P50?
Neuroreport,
12,
3303–3307Google Scholar
Yee, C.M. &
White, P.M.
(2001).
Experimental modification of P50 suppression
Psychophysiology,
38,
531–539.Google Scholar
Zachary, R.A.
(1967).
Shipley Institute of Living Scale: Revised manual.
Los Angeles:
Western Psychological Services.
Group demographics
Antipsychotic medications by category
Drugs of abuse
Panel 1a: An ERP waveform depicting normal P50 sensory gating in a selected control participant. For this participant, the peak of the P50 response to the first stimulus (S1) occurs at 62.3 ms and is 2.20 μV in amplitude. The peak of the P50 response to the second stimulus (S2) occurs at 62.3 ms and is 0.80 μV in amplitude. Thus, the P50 sensory gating ratio (S2/S1) would be .36, reflecting normal gating. Panel 1b: An ERP waveform depicting abnormal sensory gating in a patient with schizophrenia. The peak of the P50 response to the first stimulus (S1) occurs at 59.8 ms and is 2.70 μV in amplitude. The peak of the P50 response to the second stimulus (S2) occurs at 59.8 ms and is 2.07 μV in amplitude. Thus, the sensory gating ratio (S2/S1) would be .77, indicating impaired gating.
Bars represent group mean P50 Auditory Sensory Gating Ratios (S2/S1), error bars represent standard deviation. Abbreviations: Con/Neg ETOH = Control/Negative ETOH; Con/Pos ETOH = Control/Positive ETOH; Schiz/Neg ETOH = Schizophrenia/Negative ETOH; Schiz/Pos ETOH = Schizophrenia/Positive ETOH.
Bars represent group mean Executive Attention Domain Scores (summed z scores), error bars represent standard deviation.
Bars represent group mean General Memory Domain Scores, error bars represent standard deviation.
Neuropsychological test group means and significance from control/negative ETOH
You have
Access
- 21
- Cited by